Abstract
To develop an effective therapeutic strategy for cardiac regeneration using bone marrow mesenchymal stem cells (BM-MSCs), the primary mouse BM-MSCs (1st BM-MSCs) and 5th passage BM-MSCs from β-galactosidase transgenic mice were respectively intramyocardially transplanted into the acute myocardial infarction (AMI) model of wild type mice. At the 6th week, animals/tissues from the 1st BM-MSCs group, the 5th passage BM-MSCs group, control group were examined. Our results revealed that, compared to the 5th passage BM-MSCs, the 1st BM-MSCs had better therapeutic effects in the mouse MI model. The 1st BM-MSCs maintained greater differentiation potentials towards cardiomocytes or vascular endothelial cells in vitro. This is indicated by higher expressions of cardiomyocyte and vascular endothelial cell mature markers in vitro. Furthermore, we identified that 24 proteins were down-regulated and 3 proteins were up-regulated in the 5th BM-MSCs in comparison to the 1st BM-MSCs, using mass spectrometry following two-dimensional electrophoresis. Our data suggest that transplantation of the 1st BM-MSCs may be an effective therapeutic strategy for cardiac tissue regeneration following AMI, and altered protein expression profiles between the 1st BM-MSCs and 5th passage BM-MSCs may account for the difference in their maintenance of stemness and their therapeutic effects following AMI.
Highlights
Acute myocardial infarction (AMI), a main presentation of ischemic heart disease, is one leading cause of death globally
We examined the profiles of proliferation, apoptosis, and differentiation potentials towards cardiomyocytes and vascular endothelial cells of the 1st or the 5th passage BM-MSCs, and expressions of gene markers for pluripotent stem cells or tissue committed stem cells expressed by the two types of cells, and identified protein expression profiles between the 1st BM-MSCs and the 5th passage BM-MSCs
Following the treatment of 59-azacytidine, mRNA levels of desmin were downregulated while mRNA levels of troponin I were upregulated either in the 1st BM-MSCs or in the 5th BM-MSCs, and mRNA levels of MHC-b was upregulated in the 1st bone marrow mesenchymal stem cells (BMMSCs) while they remained unchanged in the 5th passage BM
Summary
Acute myocardial infarction (AMI), a main presentation of ischemic heart disease, is one leading cause of death globally. Pharmacologic intervention and coronary artery bypass grafting, which can restore the blood flow (reperfusion), keep viable myocardium working, these approaches cannot rescue dying myocardium or restore normal cardiac functions. New therapeutic approaches are needed for patients under critical conditions suffering from small vessel diffuse lesions, who are unable to withstand coronary angioplasty and for whom medication is not effective. It is imperative to develop an effective therapeutic approach to regenerating myocardium and restoring its normal contractile-relaxant function following AMI. It was commonly accepted that cardiomyocytes, as terminally differentiated cell type, could not be regenerated. Accumulated evidence indicates that cardiac muscles can be regenerated or repaired via a variety of ways including stem cell technology [1]
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